Traditional opiate receptor agonists such as morphine and fentanyl interact strongly with the μ-opioid receptor present on the surface of several types of cells in the human body. Large and/or repeated doses of a typical μ-opioid receptor agonist result in activation of a pathway to modulate the stimulus, reducing its effectiveness. The modulation pathway involves interaction of the intracellular portion of the receptor with a family of proteins called arrestins. Interaction of the arrestin with the internal portion of the receptor blocks the interaction of other molecules and stops the normal cascade of activity in the cell. In addition to this modulation, the arrestins cause the receptor to “internalize” or pucker so that it is more difficult for extracellular molecule to dock with the receptor. This modulation effectively reduces the efficacy of the drug, leading to the requirement for higher doses to achieve the same level of pain reduction.
Accordingly, it is desirable to develop alternatives to existing pain relief formulations that provide effective control of pain with lower potential for addiction. It is also desirable to identify alternative active compounds that are effective at relatively low doses of the active ingredient and are economical to incorporate into stable pharmaceutical formulations.
Salvinorin, also known as Salvinorin A, is a psychotropic molecule found naturally in Salvia divinorum and having the following structure.

A limited amount of research has been performed to identify salvinorin derivatives that may be useful for the treatment of pain. For example, U.S. Pat. No. 7,728,001 to Prisinzano et al. described a class of salvinorin derivatives that were claimed to be opioid receptor ligands. U.S. 2017/0313692 A1 by Prisinzano identified a much smaller class of salvinorin-derived compounds that are μ-opioid receptor agonists and were claimed to exhibit a significant reduction of the negative side effects commonly associated with morphine-derived compounds. In general, however, the potential of salvinorin derivative compounds to provide effective pain relief without the undesirable side effects associated with traditional opiate receptor agonists has not been studied in great detail.